Exogenous calmodulin potentiates vasodilation elicited by phospholipid-associated VIP in vivo

The purpose of this study was to determine whether exogenous calmodulin pot entiates vasoactive intestinal peptide (VIP)-induced vasodilation in vivo a nd, if so, whether this response is amplified by association of VIP with st erically stabilized liposomes. Using intravital microscopy, we found that c almodulin suffused together with aqueous and liposomal VIP did not potentia te vasodilation elicited by VIP in the in situ hamster cheek pouch. However , preincubation of calmodulin with liposomal, but not aqueous, VIP for 1 an d 2 h and overnight at 4 degrees C before suffusion significantly potentiat ed vasodilation (P < 0.05). Calmodulin-induced responses were significantly attenuated by calmidazolium, trifluoperazine, and NG-nitro-L-arginine meth yl ester (L-NAME) but not D-NAME. The effects of L-NAME were reversed by L- but not D-arginine. Indomethacin had no significant effects on calmodulin- induced responses. Calmodulin had no significant effects on adenosine-, iso proterenol-, acetylcholine-, and calcium ionophore A-23187-induced vasodila tion. Collectively, these data indicate that exogenous calmodulin amplifies vasodilation elicited by phospholipid-associated, but not aqueous, VIP in the in situ peripheral microcirculation in a specific, calmodulin active si tes-, and nitric oxide-dependent fashion. We suggest that extracellular cal modulin, phospholipids, and VIP form a novel functionally coordinated class of endogenous vasodilators.